Abstract
A new microbial secondary metabolite, paulobutalipin (1), was isolated and characterized from the culture of a mountain soil-derived Streptomyces strain. The structure of paulobutalipin (1) was elucidated through a combined analysis of spectroscopic data, single-crystal X-ray diffraction, chemical modifications including application of the modified Mosher's method, and electronic circular dichroism calculations. In an in vitro hepatocellular steatosis model induced by palmitic and oleic acids, paulobutalipin (1) reduced intracellular lipid accumulation in AML12 hepatocytes by approximately 30% compared to that of vehicle controls. Moreover, it enhanced mitochondrial abundance in a dose-dependent manner, suggesting stimulation of mitochondrial β-oxidation. Our data identify paulobutalipin as a unique microbial natural product that promotes energy metabolism possessing structural complexity and minimal toxicity.